REVIEW
PSORIATIC RESEARCH IN CHINA CHANGGENG SHAO, M.D., GANYUN YE, M.D., CHANGEA HU, M.D., AND EUREN ZHANG, M.D.
EPIDEMIOLOGY
Psoriasis is one of the most common skin diseases in the world. In 1984, a cooperative epidemiologic study of psoriasis, the first on a large scale with a uniform survey method and criteria, was carried out in the natural population of different geographic regions including northeastern, northwestern, northern, southwestern, coastal, and inland areas of China.' In a total population of 6,617,917, there were 11,393 psoriasis patients discovered. According to the different urban and rural prevalence of psoriasis in southern and northern areas, together with the populations of these areas, a total prevalence rate of 0.123% was calculated for this country. In order to make the results comparable, standardized prevalence of psoriasis for each survey spot was derived according to age groups and sex distribution of a certain sample. As a result it was found that the psoriasis prevalence was higher in tnen (0.168%), urban populations (0.176%), and the northern part of the country (0.20%), and lower in women (0.124%), rural areas (0.10%), and the south (0.14%). The annual incidence of psoriasis in 1984 was 0.012%, being one tenth of the prevalence of the same year; like tbe prevalence it was also characterized by predorninatice of psoriasis in male urban population of north China, a phenomenon warranting further discussion.^ Based on data of annual incidence, it was possible to detect age liability of different age groups; tbe age incidence of psoriasis reflects the age liability to psoriasis more exactly and reasonably than the component ratio of age at onset of disease used to do. In this survey, tbe peak incidence rate for men was in tbe 20-29 age group. The age incidence for men was lower in the 15-20 age group, but higher than women in all the other age groups.^
Among a group of 11,320 patients with psoriasis in 1984, there were 11,092 cases of psoriasis vulgaris, accounting for the overwhelming majority of the patients (97.98%), 66 cases of erythrodermic psoriasis (0.58%), 79 cases of pustular psoriasis (0.69%), 79 cases of arthropathica psoriasis (0.69%), and four cases of exudative psoriasis (0.04%). This was consistent with previously reported data on clinical type constituent ratio of psoriasis in China.' Sixty-two cases of arthropathica psoriasis (tnakitig up 0.80% of the total psoriasis patients) were found in the survey spots to the north of the 35° north latitude, while only 17 cases of arthropatbica psoriasis (0.47% of the total psoriasis patients) were found in the survey spots on the south of the 35° north latitude; the difference was statistically significant (P< 0.001).
Anthralin
Tar
Topicals
Corticosteroid
Chinese Medicinal Herb
MTX
PUVA
From the Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing; the Department of Dermatology, Wuhan First Municipal Hospital, Wuhan; and the Shandong Provincial Institute of Dermatology, Shandong, Chma. Address for correspondence: Shao Changgeng, M.D., Institute of Dermatology, Chinese Academy of Medical Sciences, 114 Jiangwangmiao Road, Taipingmen, Nanjing, China.
Oral Medication
Lei Gong Teng Figure 1. 840
Sequential form of therapy.
Retinoids
Psoriasis in Ciiina Shao ct ai.
and the susceptibility gene of psoriasis. HLA-CW6 and Ht,A-DR7 antigen frequencies in patietits with psoriasis are found to be increased, but there is no statistically significant difference between the atitigen frequencies in patients and controls.** While the association between HLA-Al, B27, and arthropathica psoriasis is well known, some authors found that the frequencies of HLA-B13 were significantly higher in psoriatic arthritis patients (peripheral type) and generalized pustular psoriasis than in healthy control groups.**•'' Still others noticed that HLA-A30-F.31,*' AW-19, CW-4, and CW-6,"''^'' A3, and AU)'' antigen frequencies in psoriatics were increased. In a family study, Shi Yan et al. determined HLA-A, and B antigens in 17 families with tnore than one patient in Jiangsu Provitice." Three relatively susceptible haplotypes to psoriasis were found by the PortaMcHugh formulas: they were A2-B13, A3-B13, and A9B5. Predisposition to psoriasis controlled by HLA-linked genes was confirmed by Nijenhuis method. The linkage analysis by Lods indicated that the susceptible gene to psoriasis was tnoderately linked with the HLA region. Cao Kai et al. and Sun Yiping et al. investigated 12 families each having at least two siblings affected by psoriasis.''*'''^ The results of Lods score for families showed that there was a linkage between the susceptible genes and HLA haplotypes; analysis of HLA antigens and clinical practice in psoriasis suggested that detertnination of HLA haplotype in suspected patients tnay help early diagnosis.
GENETICS
The etiology and pathogenesis of psoriasis are not cotnpletely understood; however, it is certain that there exists a genetic background to this condition. During the large scale survey of 1984, 4958 patients with psoriasis (including probands and their relations) distributed in 3993 families were found in 562,969 families consisting of 2,377,842 people. There were 688 families with two or tnore psoriasis patients, including 1653 patients. Therefore, 33.34% of patients with psoriasis had a positive family history. In addition, in Shanghai 55 psoriasis patients having a fatnily history were studied in 1980. They were located in 31 fatnilies consisting of 777 people. The prevalence in these families was 10.29% (men and women were 50% each), while the prevalence of the general population was only 0.298% according to a survey of 110,614 people in Shanghai. Therefore, the family prevalence of psoriasis is markedly higher than that of the natural population.'* Liu Xiyi et al.^ investigated genetic rules of psoriasis. In 7701 fatnily tnembers of 336 psoriatics, there were 83 patients (prevalence, 3.66%) derived from 2,266 persons of first degree relative of fatnily members, 26 patients (prevalence, 0.76%) from 3,268 persons of second degree relative, 13 patients (prevalence, 0.6%) from 2,167 persons of third degree relative, which indicated that the closer the relatives the higher the prevalence of psoriasis. Guo Yonglu et al.'' studied the psoriasis clustering in families. An analogy of a Poisson distribution model was performed by probability density function for 408 psoriatic families in some regions of northeast China. It was found that there was significant clustering of cases in the psoriatic families, which suggested the relation of psoriasis to genetic predisposition (susceptibility or liability) and other environmental factors. They also estimated that the heritability and standard error of psoriasis was between 38±1.2 and 48+1.2%, which was lower than that (63%) calculated by Liu Xiyi et al. in Shanghai. It is thought that psoriasis is a hereditary polygenic disease, and that environtnental factors should be considered. Psoriasis is a chronic disease, frequently having a fatnily history, tetiding to an onset iti adulthood, atid being related to environmental factors. These characteristics are often met in Ht.A-associated diseases. During the past 10 years, HLA frequency in the patients with psoriasis has been studied extensively; there have been many reports from different parts of this country.^"" In the study of population, most authors have proved the association of psoriasis vulgaris with HLAAl, B13, and til 7, in agreement with that reported from abroad. Moreover, it has been shown that HLA-B17/ HLA-A1 haplotype predisposes to psoriasis, and a linkage may exist to some extent between this haplotype
TREATMENT
During the past 10 years dermatologists have made great efforts in the treattnent of psoriasis in this country. Topical Anthralin and its derivatives. Since 1978 anthralin has been synthesized and used in clinics in China. "* Although it is effective, it has side effects: irritation of the skin, and violet-brown staining of the skin and clothitig. Attempts have been tnade to reduce the side effects. An anthralin cream was clean and easy to wash out. Patients liked the cream, although it was less effective than ointment of the same concentration.'^ Recently, a controlled trial was conducted as right-left cotnparisons, where psoriasis patients were randomized to the treatment, anthralin stick versus anthralin ointtnent. No differences between the treated sides were observed clinically, but the side effects of the stick were significantly lower than those of the ointment.'** The stick may be one of the best formulations of anthralin in the treatment of psoriasis. In 1984, the Institute of Dermatology, at the Chinese Acadetny of Medical Sciences synthesized 10acetyl anthralin and observed its effects and side ef841
International Journal of Dermatology Vol. 31, No. t2, December 1992
fects. It was found that the 10-acetyl atithraliti and anthralin had the same antipsoriatic efficacy, but the side effects of the former, especially the staining, were much less than those of the latter.'^'^° 10-Butyryl anthralin is reportedly the best of the examined 10-acyl analogues of anthralin. The Institute of Dermatology studied its effect and side effects and obtained results consistent with that of Mustakallio et al.^''^^ Short contact therapy has been reviewed in the literature.^^ In our recent experience, the anthralin side effects can be avoided by using short contact therapy instead of the conventional treatment; the effect remains utichanged.^'* Corticosteroids. Potent corticosteroids have been widely used in the treatment of psoriasis. Triamcinolone, halcinonide, clobetasol propionate generally give satisfactory results. Recently, Han Guozhu et al.^^ used CGP14 458 ointment (Ulobetasol, Ciba-Geigy), to treat 34 patients with plaque psoriasis, one application per day. All patients obtained clinical clearance in an average of 18 days, the shortest course of treatment being 6 days. Hu Zijia et al.^* studied the influence of topical use of Ulobetasol on plasrna cortisol level in patients and noticed that large area topical application (rnore than 20% body surface) or with occlusion could rnarkedly decrease the plasma cortisol level. More attention should be given to this clinical practice.
carefully restricted for only the severe cases who do not respond to conventional therapies. Chinese medicinal herbs. Since the late 1970s, Lei Gong Teng (Tripterygium wilfordii Hook f.) has given good results in the treatment of psoriasis. Qin Wanzhang^'' treated 11 patients with pustular psoriasis with Lei Gong Tetig syrup. Of these patients, 10 had sigtiificant improvement with rapid dryness and desquamation of the pustulae within 3 to 5 days. Lei Gong Teng can improve some symptotns such as fever, ar.thralgia, etc. Though patients often have a relapse when stopping the drug, it is still effective when prescribed to the patients agaiti. The Institute of Dermatology, CAMS, employed the Lei Gong Teng preparations for patients with arthropathic and erythrodermic psoriasis and received good results.^' It found that Lei Gong Teng is useful in the treatment of psoriasis vulgaris in progressive stage; it flattens the lesions, fades the coloration, decreases desquamation, and ceases the development of new lesions within 1 week after being prescribed to patients. It appears that Lei Gong Teng possesses a potent anti-inflammatory effect and has a promising prospect in the field of psoriasis treatment. It is worth further research. Chuan Bai Zhi (Angelica dahurica var. Tawainiana) is a comrnonly used Ghinese traditional medicinal herb. Chongqing Cooperative Psoriasis Research Group treated 159 patients with psoriasis with an oral preparation of this herb and black light with favorable therapeutic results. This preparation, containing furocoLimarin analogues such as imperatorin and isoirnperatorin, was similar to 8-MOl' in curative effect, but its side effects were milder than that of 8-methoxypsoralen (8-MOP). The research group suggests that Chuan Bai Zhi is a valuable herb for treatitig psoriasis.'^
Topical use of Chinese medicinal herbs. Wang Shumin^'' treated 100 cases of psoriasis with compound ointment of camptothecin; 64 cases showed complete clearance of lesions, 12 cases showed evident improvemetit, and 23 cases showed improvemetit. Liti Xiran et al.^** found satisfactory results in treating 101 cases of psoriasis with camptotheca acuminata tincture. Indirubin^** and triptolidenol'" topicals were prepared for psoriasis; they are effective, and worth investigating further.
Others Oral Medication
Erythromycin, and ketoconazole are also recomtnended in the treatment of psoriasis, for these antimicrobials can eliminate the focal infections that are probably the precipitating factors of disease. Psoriasis can be improved to a certain extent by acupuncture treattnent in some cases.^^"^^ The cause and triggering factors of psoriasis are not clear. The result of therapeutic effects of any modalities is temporary. Therefore, the treattnent has to be aitned at comprehensively using the methods available, raising the therapeutic effect, prolonging the remission period, and decreasing the side effects as much as possible. For this reason we suggest the following principles. Therapy according to the clinical types of disease. There is no therapy which is effective for all types of psoriasis. Different types (stages) need different methods of treatment. For example, psoriasis guttata, associated with infection factors as a rule, necessitates the
Antineoplastics. Many kinds of antineoplastics have been used for the treatment of psoriasis for more than 30 years; aminopterin, methotrexate (MTX), hydroxyurea, bleomycin, azathioprine, ethylirnin, bimolane, and camptothecin have been employed successfully.'' Most authors consider that they are effective but, owing to their side effects, cannot be chosen as firstline drugs. A follow-up study oi 113 outpatients with psoriasis was reported by Peng Yongnian et al.''^ It revealed that the severity of the disease was markedly related to the course of the disease and also the anticancer drugs used. The authors made a retrospective cohort study to confirm that the patients who had used aminopteriti or busulfan became deteriorative as compared with the controls. Some patients due to longterm administration of this kind of drug developed leukemia.-*^ Therefore, the use of these drugs should be 842
Psoriasis in China Shao et al.
use of antibiotics, also UVB often has a good response; while for localized plaque lesions, bigh concentration antbralin or potent corticosteroids are desirable; for generalized or some special types of psoriasis, cytotoxic drugs, retinoids, or Lei Gong Teng preparations and PUVA are needed. Sequential form of therapy. Because every medicine (or therapy) bas its advantages and disadvantages, prolonged use of a tberapy can cause not only tbe decrease of its effects, but tbe accumulation of its toxicities. Tberefore, several effective metbods of treatment could be prescribed alternately, keeping tbe response and decreasing the side effects (Fig. 1). Combination therapies. The clinical manifestations of psoriasis are various. For some types of the disease a single tberapy cannot clear the lesions completely. Tbe combination of two or more drugs or metbods is necessary. The following regimens bave been used effectively: (1) retinoids plus PUVA; (2) Lei Gong Tetig plus MTX; (3) PUVA plus anthralin (or corticosteroids); (4) MTX plus PUVA plus antbralin; (5) retinoids plus MTX. Fry, tbe British dermatologist, wrote in the centenary of the birtb of tbe British Journal of Dermatology as follows: "Psoriasis is not only amenable to treatment, but curable." The above quotation is taken from the first report on psoriasis published in the first volume of the British Journal of Dermatology 100 years ago. Unfortunately, time has shown that this statement was not true then, and it is still not true in 1988. Fry continued tbat whatever the future reveals, bopefuliy the claims made in tbe first volume of tbe British Journal of Dermatology will prove correct in the next 100 years.'*" We have the same idea, and hope we can make our contribution to researcb for tbe cure of psoriasis.
8. 9. 10.
Song FJ, Xu SY, Li HG, et al. HLA antigens and psoriasis. Chin J Dermatol 1987; 20:288-289. Xia JZ, Xu H, Xu B, et al. HLA and psoriasis. J Clin Dermatol 1983; 12:3-4. Xu XP, Zheng CY, Li QH, et al. Study on the association of HLA with psoriasis vulgaris. Chin J Dermatol 1985; 18:158-159.
11.
Wang ZH, Zhang BY, Li XA, et al. Study on the association of HLA with psoriasis. Chin ] Dermatol 1988; 21:305-306.
12.
Shi SY, Yan YP. An investigation of HLA in psoriatic arthritis and rheumatoid arthritis patients. J Clin Dermatol 1988; 17:226-228.
13.
Shi Y, Ma L Wang HQ, et al. Study of correlation of psoriasis with HLA. Chin J Dermatol 1990; 23:230-233. Cao K, Song FJ, Li HG, et al. Study of association between HLA and psoriasis vulgaris. Chin J Dermatol 1990; 23:381-383.
14.
15.
16. 17.
Sun YP, An JB, Chen WC, et al. A study on the linkage between HLA and susceptibility gene of psoriasis. Natl Med J Chin 1986; 66:600-604. Shao CG. Advances in anthralin research. J Clin Dermatol 1983; 12:316-318. Shao CG, Huang WL, Ma HS, et al. Treatment of psoriasis with anthralin cream and bath and ultraviolet irradiation. J Clin Dermatol 1982; 11:16-17.
18.
Zhang FR, Shao CG, Ma DM, et al. Treatment of psoriasis with anthralin stick: a controlled trial. J Clin Dermatol 1991; 20:247-248.
19.
Ma DM, Wang LL. Synthesis of 10-acetylanthralin. Pharm Indus 1984; 10:4-5.
20.
Shao CG, Ma DM, Wang LL, et al. A study of the antipsoriatic comparative efficacy of 10-acetylanthralin ointment and anthralin ointment. J Clin Dermarol 1984; 13:12-13.
21.
Zhang FR. Treatment of psoriasis with 10-butyryl anthralin (Butantron) stick: a controlled trial. (Unpublished). Mustakallio KK, Brandt H, Halmekoski I, et al. Butantrone, a less toxic and less stainitig substitute for dithranol(anthralin). Acta Derm Venereol [suppl](Stockh) 1984; 113:156-157. Tan ZK. Recent advances in treatment of psoriasis with anthralin: short contact therapy. Foreign Medicine Derm Sec 1987; 3:129-131.
22. REFERENCES
1.
Cooperative Psoriasis Study Group. Distribution of psoriasis in China: a nation-wide screening in t984. Chin J Dermatol 1986; 19:253-261.
23.
2.
Zhang GW, Shao CG, Wang GC. Annual incidence and age-liability of psoriasis in China. Chin J Dermatol 1987; 20:129-134.
24.
Zhang FR. A controlled study of short contact therapy with anthralin stick vs conventional anthralin treatment (Unpublished).
3.
Li HJ. Psoriasis in China. Chin Med J 1982; 95: 245-256.
25.
4.
Zhou DY, Zheng MR. Study on genetic factors in psoriasis: a preliminary report. Chin J Dermatol 1980; 13:64-66.
Han GZ Shao CG, Gu H, et al. Treatment of psoriasis with CGP14 458 ointment. Chin ) Dermatol 1987; 20:283. Hu ZJ, Jin PY, Yue XY, et al. Treatment of psoriasis with 0.05% CGP14 458 ointment: observation of clinical effect and plasma corticosteroid levels. Chin J Dermatol 1988; 21:291-292. Wang SM. Treatment of psoriasis with compound ointment of camptotheca acuminata: a report of 100 cases. Jilin Med 1983; 4:24.
5.
Liu XY, Rui JX. Study on the generic trend in psoriasis vulgaris. Chin J Dermatol 1982; 15:11-13.
6.
Guo YL, Jiang SX. Investigation of heritability of psoriasis and its clustering in the family. Chin ] Dermatol 1986; 19:325-326.
7.
Song FJ, Chen YH, Liu ZY, et al. HLA antigens and psoriasis. Chin J Dermatol 1981; 14:191-194.
26.
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28.
843
Li XR, Huang T. Clinical observation and experimental study on the effect of camptotheca acuminata tincture in treating psoriasis. Chin J Dermatol 1982; 15:210-212.
Intcriiationai Journai of Dermatoiogy Voi. 31, No. 12, Dcccmiier 1992
29.
30.
31.
32. 33.
34.
35. Lei Gong Teng Study Group, Chinese Academy of Medical Sciences. Lei Gong Teng (Trypterygimn wilfordii Hook.) total glucosides: study of its therapeutic effect in certain dermatoses. Chin J Dermatoi 1982; 15:199-201. 36. Chongqing Cooperative Psoriasis Research Group. Treatment of psoriasis with oral preparations of Ghuan Bai Zhi and black light: a report of therapeutic effect in 159 patients. Chin J Dermatoi 1981; 14:129-131. 37. Li YQ, Song R, Sun WH, et al. Treatment of psoriasis with erythromycin: a paired comparison. Chin J Dermatoi 1989; 22:181-182. 38. Tan JQ, Guo NR, Wu SX. Treatment of psoriasis with ketoconazole: an observation of therapeutic effect in 19 cases. J Clin Dermatoi 1990; 19:302. ?>9. Gu XX. Acupuncture therapy for 25 cases of psoriasis: analysis of therapeutic effect. Shanghai I Acupuncture 1982; 3:4. 40. Fry L. Psoriasis. Br J Dermatoi 1988; 119:445-461.
Zhou JF, Zhong YZ, Tang DS. Dingshu T. Investigation on the topical treatment with indiruhin in psoriasis Chin J Dermatoi 1982; 1.5:225-226. Shanghai Cooperative Group of Psoriasis Treatment with Triptolidcnol Ointment. Treatment of psoriasis with triptolidenol ointment. Chin J Dermatoi 1988; 21:381-382. Psoriasis Research Group, Beijing Medical College. Chemotherapy for psoriasis. Chin J Dermatoi 1980; 13: 61-63. Peng YN, Jiang JJ, Qin SD. A follow-up study of 213 cases of psoriasis. Chin J Dermatoi 1983; 16: 207-210. Huang WX, Li HZ, Zhang A. Two cases of acute myeloblast leukemia following treatment of psoriasis with ethyliminum. Chin J Dermatoi 1985; 18:39. Qin WZ. Advances in the study on clinical effects of Tripterygium wilfordii and Begonia yunnanensis. Shang-
hai J Traditional Chin Med Drugs 1981; 4:46^8.
Evidence of Food Deficiency Diseases Almost four centuries before the pronouncements of Funk, Hopkins, and Pekelharing, scurvy and its cure were clearly described. When Jacques Cartier had three ships immobilized in the ice in the St. Lawrence River during the winter of 1535-36 his crews were severely stricken by the disease. Almost the whole crew was suffering from lassitude, swollen and blackened limbs, sore gums and loosening teeth, and hemorrhages. An autopsy performed on the first man who died revealed a white and shriveled heart, lungs black and gangrenous, and evidence of severe internal hemorrhages. From the local Indians Cartier learned to prepare an infusion from the bark and leaves of a tree named Annedda in his journal. The stricken men drank the unpleasant brew and poured it on their legs. Recoveries were miraculously rapid. It is presumed that the tree was the Canadian fir whose needles have been found to contain a substantial amount of ascorbic acid. Two centuries later the Scottish ship surgeon James Lind persuasively demonstrated that scurvy can be cured by administration of the juice of fresh oranges and lemons. In 1746, aboard the Salisbury, he treated six pairs of scorbutic sailors with standard remedies. Two sailors treated with oranges and lemons showed rapid recovery. The ten receiving other remedies (cider, vinegar, seawater, sulfuric acid, or an antiscorbutic electuary) showed no improvement except possibly the two who received a quart of cider daily. In his book, A Treatise on the Scurvy, Lind not only described his experiments but presented a history of the disease which revealed the value of fresh fruits and vegetables in its treatment and prevention. When Captain James Cook embarked on his second voyage of exploration in 1772 he heeded Lind's teachings by seeing that his crew was provided with fresh fruits and vegetables. During the three-year voyage only one crewman aboard the Resolution was lost to scurvy, a striking contrast to the heavy losses customarily suffered on long sea voyages, or during prolonged sieges on land. Although Lind, who became Physician-in-Charge of the Haslar Naval Hospital at Portsmouth in 1758, campaigned for reform of the British naval diet, the Admiralty resisted his doctrines, and it was only in 1795, the year after Lind's death, that lemon juice became a required component of the sailor's diet. Because of problems associated with preservation and adulteration, the lemon juice failed to uniformly prevent scurvy and many medical officers lacked confidence in its use. Furthermore, the lime was looked upon as the equivalent of the lemon, and lime juice had official sanction for use in place of lemon juice. Lime juice, however, contains a lower level of ascorbic acid and is a less effective antiscorbutic agent. From Ihde AJ, Becker SL. Conflict of concepts in early vitamin studies. ] Hist Biol 1971; 4(i):l—33. 844
PSORIATIC RESEARCH IN CHINA CHANGGENG SHAO, M.D., GANYUN YE, M.D., CHANGEA HU, M.D., AND EUREN ZHANG, M.D.
EPIDEMIOLOGY
Psoriasis is one of the most common skin diseases in the world. In 1984, a cooperative epidemiologic study of psoriasis, the first on a large scale with a uniform survey method and criteria, was carried out in the natural population of different geographic regions including northeastern, northwestern, northern, southwestern, coastal, and inland areas of China.' In a total population of 6,617,917, there were 11,393 psoriasis patients discovered. According to the different urban and rural prevalence of psoriasis in southern and northern areas, together with the populations of these areas, a total prevalence rate of 0.123% was calculated for this country. In order to make the results comparable, standardized prevalence of psoriasis for each survey spot was derived according to age groups and sex distribution of a certain sample. As a result it was found that the psoriasis prevalence was higher in tnen (0.168%), urban populations (0.176%), and the northern part of the country (0.20%), and lower in women (0.124%), rural areas (0.10%), and the south (0.14%). The annual incidence of psoriasis in 1984 was 0.012%, being one tenth of the prevalence of the same year; like tbe prevalence it was also characterized by predorninatice of psoriasis in male urban population of north China, a phenomenon warranting further discussion.^ Based on data of annual incidence, it was possible to detect age liability of different age groups; tbe age incidence of psoriasis reflects the age liability to psoriasis more exactly and reasonably than the component ratio of age at onset of disease used to do. In this survey, tbe peak incidence rate for men was in tbe 20-29 age group. The age incidence for men was lower in the 15-20 age group, but higher than women in all the other age groups.^
Among a group of 11,320 patients with psoriasis in 1984, there were 11,092 cases of psoriasis vulgaris, accounting for the overwhelming majority of the patients (97.98%), 66 cases of erythrodermic psoriasis (0.58%), 79 cases of pustular psoriasis (0.69%), 79 cases of arthropathica psoriasis (0.69%), and four cases of exudative psoriasis (0.04%). This was consistent with previously reported data on clinical type constituent ratio of psoriasis in China.' Sixty-two cases of arthropathica psoriasis (tnakitig up 0.80% of the total psoriasis patients) were found in the survey spots to the north of the 35° north latitude, while only 17 cases of arthropatbica psoriasis (0.47% of the total psoriasis patients) were found in the survey spots on the south of the 35° north latitude; the difference was statistically significant (P< 0.001).
Anthralin
Tar
Topicals
Corticosteroid
Chinese Medicinal Herb
MTX
PUVA
From the Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing; the Department of Dermatology, Wuhan First Municipal Hospital, Wuhan; and the Shandong Provincial Institute of Dermatology, Shandong, Chma. Address for correspondence: Shao Changgeng, M.D., Institute of Dermatology, Chinese Academy of Medical Sciences, 114 Jiangwangmiao Road, Taipingmen, Nanjing, China.
Oral Medication
Lei Gong Teng Figure 1. 840
Sequential form of therapy.
Retinoids
Psoriasis in Ciiina Shao ct ai.
and the susceptibility gene of psoriasis. HLA-CW6 and Ht,A-DR7 antigen frequencies in patietits with psoriasis are found to be increased, but there is no statistically significant difference between the atitigen frequencies in patients and controls.** While the association between HLA-Al, B27, and arthropathica psoriasis is well known, some authors found that the frequencies of HLA-B13 were significantly higher in psoriatic arthritis patients (peripheral type) and generalized pustular psoriasis than in healthy control groups.**•'' Still others noticed that HLA-A30-F.31,*' AW-19, CW-4, and CW-6,"''^'' A3, and AU)'' antigen frequencies in psoriatics were increased. In a family study, Shi Yan et al. determined HLA-A, and B antigens in 17 families with tnore than one patient in Jiangsu Provitice." Three relatively susceptible haplotypes to psoriasis were found by the PortaMcHugh formulas: they were A2-B13, A3-B13, and A9B5. Predisposition to psoriasis controlled by HLA-linked genes was confirmed by Nijenhuis method. The linkage analysis by Lods indicated that the susceptible gene to psoriasis was tnoderately linked with the HLA region. Cao Kai et al. and Sun Yiping et al. investigated 12 families each having at least two siblings affected by psoriasis.''*'''^ The results of Lods score for families showed that there was a linkage between the susceptible genes and HLA haplotypes; analysis of HLA antigens and clinical practice in psoriasis suggested that detertnination of HLA haplotype in suspected patients tnay help early diagnosis.
GENETICS
The etiology and pathogenesis of psoriasis are not cotnpletely understood; however, it is certain that there exists a genetic background to this condition. During the large scale survey of 1984, 4958 patients with psoriasis (including probands and their relations) distributed in 3993 families were found in 562,969 families consisting of 2,377,842 people. There were 688 families with two or tnore psoriasis patients, including 1653 patients. Therefore, 33.34% of patients with psoriasis had a positive family history. In addition, in Shanghai 55 psoriasis patients having a fatnily history were studied in 1980. They were located in 31 fatnilies consisting of 777 people. The prevalence in these families was 10.29% (men and women were 50% each), while the prevalence of the general population was only 0.298% according to a survey of 110,614 people in Shanghai. Therefore, the family prevalence of psoriasis is markedly higher than that of the natural population.'* Liu Xiyi et al.^ investigated genetic rules of psoriasis. In 7701 fatnily tnembers of 336 psoriatics, there were 83 patients (prevalence, 3.66%) derived from 2,266 persons of first degree relative of fatnily members, 26 patients (prevalence, 0.76%) from 3,268 persons of second degree relative, 13 patients (prevalence, 0.6%) from 2,167 persons of third degree relative, which indicated that the closer the relatives the higher the prevalence of psoriasis. Guo Yonglu et al.'' studied the psoriasis clustering in families. An analogy of a Poisson distribution model was performed by probability density function for 408 psoriatic families in some regions of northeast China. It was found that there was significant clustering of cases in the psoriatic families, which suggested the relation of psoriasis to genetic predisposition (susceptibility or liability) and other environmental factors. They also estimated that the heritability and standard error of psoriasis was between 38±1.2 and 48+1.2%, which was lower than that (63%) calculated by Liu Xiyi et al. in Shanghai. It is thought that psoriasis is a hereditary polygenic disease, and that environtnental factors should be considered. Psoriasis is a chronic disease, frequently having a fatnily history, tetiding to an onset iti adulthood, atid being related to environmental factors. These characteristics are often met in Ht.A-associated diseases. During the past 10 years, HLA frequency in the patients with psoriasis has been studied extensively; there have been many reports from different parts of this country.^"" In the study of population, most authors have proved the association of psoriasis vulgaris with HLAAl, B13, and til 7, in agreement with that reported from abroad. Moreover, it has been shown that HLA-B17/ HLA-A1 haplotype predisposes to psoriasis, and a linkage may exist to some extent between this haplotype
TREATMENT
During the past 10 years dermatologists have made great efforts in the treattnent of psoriasis in this country. Topical Anthralin and its derivatives. Since 1978 anthralin has been synthesized and used in clinics in China. "* Although it is effective, it has side effects: irritation of the skin, and violet-brown staining of the skin and clothitig. Attempts have been tnade to reduce the side effects. An anthralin cream was clean and easy to wash out. Patients liked the cream, although it was less effective than ointment of the same concentration.'^ Recently, a controlled trial was conducted as right-left cotnparisons, where psoriasis patients were randomized to the treatment, anthralin stick versus anthralin ointtnent. No differences between the treated sides were observed clinically, but the side effects of the stick were significantly lower than those of the ointment.'** The stick may be one of the best formulations of anthralin in the treatment of psoriasis. In 1984, the Institute of Dermatology, at the Chinese Acadetny of Medical Sciences synthesized 10acetyl anthralin and observed its effects and side ef841
International Journal of Dermatology Vol. 31, No. t2, December 1992
fects. It was found that the 10-acetyl atithraliti and anthralin had the same antipsoriatic efficacy, but the side effects of the former, especially the staining, were much less than those of the latter.'^'^° 10-Butyryl anthralin is reportedly the best of the examined 10-acyl analogues of anthralin. The Institute of Dermatology studied its effect and side effects and obtained results consistent with that of Mustakallio et al.^''^^ Short contact therapy has been reviewed in the literature.^^ In our recent experience, the anthralin side effects can be avoided by using short contact therapy instead of the conventional treatment; the effect remains utichanged.^'* Corticosteroids. Potent corticosteroids have been widely used in the treatment of psoriasis. Triamcinolone, halcinonide, clobetasol propionate generally give satisfactory results. Recently, Han Guozhu et al.^^ used CGP14 458 ointment (Ulobetasol, Ciba-Geigy), to treat 34 patients with plaque psoriasis, one application per day. All patients obtained clinical clearance in an average of 18 days, the shortest course of treatment being 6 days. Hu Zijia et al.^* studied the influence of topical use of Ulobetasol on plasrna cortisol level in patients and noticed that large area topical application (rnore than 20% body surface) or with occlusion could rnarkedly decrease the plasma cortisol level. More attention should be given to this clinical practice.
carefully restricted for only the severe cases who do not respond to conventional therapies. Chinese medicinal herbs. Since the late 1970s, Lei Gong Teng (Tripterygium wilfordii Hook f.) has given good results in the treatment of psoriasis. Qin Wanzhang^'' treated 11 patients with pustular psoriasis with Lei Gong Tetig syrup. Of these patients, 10 had sigtiificant improvement with rapid dryness and desquamation of the pustulae within 3 to 5 days. Lei Gong Teng can improve some symptotns such as fever, ar.thralgia, etc. Though patients often have a relapse when stopping the drug, it is still effective when prescribed to the patients agaiti. The Institute of Dermatology, CAMS, employed the Lei Gong Teng preparations for patients with arthropathic and erythrodermic psoriasis and received good results.^' It found that Lei Gong Teng is useful in the treatment of psoriasis vulgaris in progressive stage; it flattens the lesions, fades the coloration, decreases desquamation, and ceases the development of new lesions within 1 week after being prescribed to patients. It appears that Lei Gong Teng possesses a potent anti-inflammatory effect and has a promising prospect in the field of psoriasis treatment. It is worth further research. Chuan Bai Zhi (Angelica dahurica var. Tawainiana) is a comrnonly used Ghinese traditional medicinal herb. Chongqing Cooperative Psoriasis Research Group treated 159 patients with psoriasis with an oral preparation of this herb and black light with favorable therapeutic results. This preparation, containing furocoLimarin analogues such as imperatorin and isoirnperatorin, was similar to 8-MOl' in curative effect, but its side effects were milder than that of 8-methoxypsoralen (8-MOP). The research group suggests that Chuan Bai Zhi is a valuable herb for treatitig psoriasis.'^
Topical use of Chinese medicinal herbs. Wang Shumin^'' treated 100 cases of psoriasis with compound ointment of camptothecin; 64 cases showed complete clearance of lesions, 12 cases showed evident improvemetit, and 23 cases showed improvemetit. Liti Xiran et al.^** found satisfactory results in treating 101 cases of psoriasis with camptotheca acuminata tincture. Indirubin^** and triptolidenol'" topicals were prepared for psoriasis; they are effective, and worth investigating further.
Others Oral Medication
Erythromycin, and ketoconazole are also recomtnended in the treatment of psoriasis, for these antimicrobials can eliminate the focal infections that are probably the precipitating factors of disease. Psoriasis can be improved to a certain extent by acupuncture treattnent in some cases.^^"^^ The cause and triggering factors of psoriasis are not clear. The result of therapeutic effects of any modalities is temporary. Therefore, the treattnent has to be aitned at comprehensively using the methods available, raising the therapeutic effect, prolonging the remission period, and decreasing the side effects as much as possible. For this reason we suggest the following principles. Therapy according to the clinical types of disease. There is no therapy which is effective for all types of psoriasis. Different types (stages) need different methods of treatment. For example, psoriasis guttata, associated with infection factors as a rule, necessitates the
Antineoplastics. Many kinds of antineoplastics have been used for the treatment of psoriasis for more than 30 years; aminopterin, methotrexate (MTX), hydroxyurea, bleomycin, azathioprine, ethylirnin, bimolane, and camptothecin have been employed successfully.'' Most authors consider that they are effective but, owing to their side effects, cannot be chosen as firstline drugs. A follow-up study oi 113 outpatients with psoriasis was reported by Peng Yongnian et al.''^ It revealed that the severity of the disease was markedly related to the course of the disease and also the anticancer drugs used. The authors made a retrospective cohort study to confirm that the patients who had used aminopteriti or busulfan became deteriorative as compared with the controls. Some patients due to longterm administration of this kind of drug developed leukemia.-*^ Therefore, the use of these drugs should be 842
Psoriasis in China Shao et al.
use of antibiotics, also UVB often has a good response; while for localized plaque lesions, bigh concentration antbralin or potent corticosteroids are desirable; for generalized or some special types of psoriasis, cytotoxic drugs, retinoids, or Lei Gong Teng preparations and PUVA are needed. Sequential form of therapy. Because every medicine (or therapy) bas its advantages and disadvantages, prolonged use of a tberapy can cause not only tbe decrease of its effects, but tbe accumulation of its toxicities. Tberefore, several effective metbods of treatment could be prescribed alternately, keeping tbe response and decreasing the side effects (Fig. 1). Combination therapies. The clinical manifestations of psoriasis are various. For some types of the disease a single tberapy cannot clear the lesions completely. Tbe combination of two or more drugs or metbods is necessary. The following regimens bave been used effectively: (1) retinoids plus PUVA; (2) Lei Gong Tetig plus MTX; (3) PUVA plus anthralin (or corticosteroids); (4) MTX plus PUVA plus antbralin; (5) retinoids plus MTX. Fry, tbe British dermatologist, wrote in the centenary of the birtb of tbe British Journal of Dermatology as follows: "Psoriasis is not only amenable to treatment, but curable." The above quotation is taken from the first report on psoriasis published in the first volume of the British Journal of Dermatology 100 years ago. Unfortunately, time has shown that this statement was not true then, and it is still not true in 1988. Fry continued tbat whatever the future reveals, bopefuliy the claims made in tbe first volume of tbe British Journal of Dermatology will prove correct in the next 100 years.'*" We have the same idea, and hope we can make our contribution to researcb for tbe cure of psoriasis.
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Evidence of Food Deficiency Diseases Almost four centuries before the pronouncements of Funk, Hopkins, and Pekelharing, scurvy and its cure were clearly described. When Jacques Cartier had three ships immobilized in the ice in the St. Lawrence River during the winter of 1535-36 his crews were severely stricken by the disease. Almost the whole crew was suffering from lassitude, swollen and blackened limbs, sore gums and loosening teeth, and hemorrhages. An autopsy performed on the first man who died revealed a white and shriveled heart, lungs black and gangrenous, and evidence of severe internal hemorrhages. From the local Indians Cartier learned to prepare an infusion from the bark and leaves of a tree named Annedda in his journal. The stricken men drank the unpleasant brew and poured it on their legs. Recoveries were miraculously rapid. It is presumed that the tree was the Canadian fir whose needles have been found to contain a substantial amount of ascorbic acid. Two centuries later the Scottish ship surgeon James Lind persuasively demonstrated that scurvy can be cured by administration of the juice of fresh oranges and lemons. In 1746, aboard the Salisbury, he treated six pairs of scorbutic sailors with standard remedies. Two sailors treated with oranges and lemons showed rapid recovery. The ten receiving other remedies (cider, vinegar, seawater, sulfuric acid, or an antiscorbutic electuary) showed no improvement except possibly the two who received a quart of cider daily. In his book, A Treatise on the Scurvy, Lind not only described his experiments but presented a history of the disease which revealed the value of fresh fruits and vegetables in its treatment and prevention. When Captain James Cook embarked on his second voyage of exploration in 1772 he heeded Lind's teachings by seeing that his crew was provided with fresh fruits and vegetables. During the three-year voyage only one crewman aboard the Resolution was lost to scurvy, a striking contrast to the heavy losses customarily suffered on long sea voyages, or during prolonged sieges on land. Although Lind, who became Physician-in-Charge of the Haslar Naval Hospital at Portsmouth in 1758, campaigned for reform of the British naval diet, the Admiralty resisted his doctrines, and it was only in 1795, the year after Lind's death, that lemon juice became a required component of the sailor's diet. Because of problems associated with preservation and adulteration, the lemon juice failed to uniformly prevent scurvy and many medical officers lacked confidence in its use. Furthermore, the lime was looked upon as the equivalent of the lemon, and lime juice had official sanction for use in place of lemon juice. Lime juice, however, contains a lower level of ascorbic acid and is a less effective antiscorbutic agent. From Ihde AJ, Becker SL. Conflict of concepts in early vitamin studies. ] Hist Biol 1971; 4(i):l—33. 844
